Modulation of Gingival Fibroblast Minocycline Accumulation by Biological Mediators

• Published in: Journal of dental research Vol. 84; no. 4; pp. 320 - 323
• Main Authors: Walters, J.D., Nakkula, R.J., Maney, P.
• Format: Journal Article
• Language: English
• Published: United States SAGE Publications 01-04-2005; SAGE PUBLICATIONS, INC
• Subjects: Adult; Analysis of Variance; Anti-Bacterial Agents - pharmacokinetics; Biological Availability; Biological Transport - drug effects; Fibroblasts - metabolism; Gingiva - cytology; Gingiva - metabolism; Growth Substances - pharmacology; Humans; Male; Minocycline - pharmacokinetics; Protein Kinase C - metabolism; Tetradecanoylphorbol Acetate - pharmacology; Up-Regulation; aggressive periodontitis; matrix metalloproteinases; tetracyclines; antimicrobial chemotherapy
• ISSN: 0022-0345; 1544-0591
• DOI: 10.1177/154405910508400405

Gingival fibroblasts actively accumulate tetracyclines, thereby enhancing their redistribution from blood to gingiva. Since growth factors and pro-inflammatory cytokines regulate many fibroblast activities, they could potentially enhance fibroblast minocycline accumulation. To test this hypothesis, we treated gingival fibroblast monolayers for 1 or 6 hours with platelet-derived growth factor-BB (PDGF), fibroblast growth factor-2 (FGF), transforming growth factor-β1 (TGF), or tumor necrosis factor-α (TNF). Minocycline uptake was assayed at 37° by a fluorescence method. All 4 factors significantly enhanced minocycline uptake (P ≤ 0.008, ANOVA), primarily by increasing the affinity of transport. Treatment for 6 hours with 10 ng/mL FGF, PDGF, TGF, or TNF enhanced fibroblast minocycline uptake by 19% to 25%. Phorbol myristate acetate enhanced fibroblast minocycline uptake by 28%, suggesting that protein kinase C plays a role in up-regulating transport. These effects on transport provide a mechanism by which systemic tetracyclines could be preferentially distributed to gingival wound or inflammatory sites.